The nuclear export inhibitor selinexor improves kidney function in a rat model of focal segmental glomerulosclerosis

American Journal of Physiology-Renal Physiology, vol. 329, pp. F496–F509

Abstract

Focal segmental glomerulosclerosis (FSGS) involves podocyte injury, potentially linked to dysfunctional nuclear pore complexes (NPCs). We show that selinexor (KPT-330), a nuclear export inhibitor, restores NPC function in vitro. In an FSGS rat model, selinexor improves kidney function, lowers serum creatinine and cystatin C levels, and reduces serum lipid levels. However, histological damage persists, indicating partial but not complete protection. These findings highlight NPC-targeted therapies as a potential strategy for treating FSGS.

Authors 14

1. Yingying Gao Aachen Division of Nephrology and Clinical Immunology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   RWTH University Clinic

   Division of Nephrology and Clinical Immunology, RWTH University Clinic, Aachen, Germany

2. Ina Verena Martin Aachen Division of Nephrology and Clinical Immunology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   RWTH University Clinic

   Division of Nephrology and Clinical Immunology, RWTH University Clinic, Aachen, Germany

3. Ute Raffetseder Aachen Division of Nephrology and Clinical Immunology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   RWTH University Clinic

   Division of Nephrology and Clinical Immunology, RWTH University Clinic, Aachen, Germany

4. Xiyang Liu Aachen Division of Nephrology and Clinical Immunology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   RWTH University Clinic

   Division of Nephrology and Clinical Immunology, RWTH University Clinic, Aachen, Germany

5. Anna Leitz Aachen Division of Nephrology and Clinical Immunology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   RWTH University Clinic

   Division of Nephrology and Clinical Immunology, RWTH University Clinic, Aachen, Germany

6. Marcus Johannes Moeller Aachen Division of Nephrology and Clinical Immunology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   RWTH University Clinic

   Division of Nephrology and Clinical Immunology, RWTH University Clinic, Aachen, Germany

7. Eleni Stamellou Aachen Division of Nephrology and Clinical Immunology

   University of Ioannina · Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   RWTH University Clinic

   University of Ioannina

   Department of Nephrology, School of Medicine, University of Ioannina, Ioannina, Greece

   Division of Nephrology and Clinical Immunology, RWTH University Clinic, Aachen, Germany

8. Ramona Jühlen Aachen Institute of Biochemistry and Molecular Cell Biology Medical School

   RWTH Aachen University

   Affiliation as printed

   RWTH Aachen University

   Institute of Biochemistry and Molecular Cell Biology, Medical School, RWTH Aachen University, Aachen, Germany

9. Angela Martina Schulz

   Charité - Universitätsmedizin Berlin

   Affiliation as printed

   Charité-Universitätsmedizin Berlin

10. Reinhold Kreutz

    Charité - Universitätsmedizin Berlin

    Affiliation as printed

    Charité-Universitätsmedizin Berlin

11. Jürgen Floege Aachen Department of Cardiology Division of Nephrology and Clinical Immunology

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    RWTH University Clinic

    Department of Cardiology, RWTH University Clinic, Aachen, Germany

    Division of Nephrology and Clinical Immunology, RWTH University Clinic, Aachen, Germany

12. Rafael Kramann Aachen Division of Nephrology and Clinical Immunology

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    RWTH University Clinic

    Division of Nephrology and Clinical Immunology, RWTH University Clinic, Aachen, Germany

13. Wolfram Antonin corresponding Aachen Institute of Biochemistry and Molecular Cell Biology Medical School

    RWTH Aachen University

    Affiliation as printed

    RWTH Aachen University

    Institute of Biochemistry and Molecular Cell Biology, Medical School, RWTH Aachen University, Aachen, Germany

14. Tammo Ostendorf corresponding Aachen Division of Nephrology and Clinical Immunology

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    RWTH University Clinic

    Division of Nephrology and Clinical Immunology, RWTH University Clinic, Aachen, Germany